CSF refers to a family of lymphokines which induce progenitor cells found in the bone marrow to differentiate into specific types of mature blood cells. The particular type of mature blood cell that results from a progenitor cell depends upon the type of CSF present. For instance, erythropoietin is believed to cause progenitor cells to mature into erythrocytes, while thrombopoietin is thought to drive progenitor cells along the thrombocytic pathway. Similarly, granulocyte-macrophage colony formation is dependent on the presence of GM-CSF. The present invention concerns an analog of human GM-CSF.
CSF, including human GM-CSF, is produced only in minute quantities in vivo. CSF-like factors have been extracted from body organs, Sheridan and Stanley, J. Cell. Physiol., 78:451-459 (1971), and have been detected in serum and urine, Robinson et al., J. Cell. Physiol., 69:83-92 (1967); Stanley et al., J. Lab. Clin. Med., 79:657-668 (1972). Researchers have reported isolating low titer CSF-like factor from human peripheral blood cells which appear to be macrophages or monocytes, Moore and Williams, J. Cell. Physiol., 80:195-206 (1972); Golde and Kline, J. Clin. Invest., 51:2981-2983 (1972); Moore et al., J. Natl. Cancer Inst., 50:591-601 (1973).
Although the factors identified by the above researchers have been reported to be CSF, heretofore sufficient quantities of homogeneous human CSF, including GM-CSF, have not been available to thoroughly investigate its biochemistry and biology. The availability of adequate quantities of homogeneous human GM-CSF would be valuable in investigations and possible treatment of proliferative blood disorders, such as certain leukemias and anemias. Also, human GM-CSF in greater purity and larger quantities than heretofore available could prove useful in achieving successful bone marrow transplantation following cancer chemotherapy.
One potential method of providing larger quantities of homogeneous polypeptides including human GM-CSF than heretofore available is through recombinant DNA techniques. Recombinant DNA techniques have been developed for economically producing a desired protein once the gene coding for the protein has been isolated and identified. A discussion of such recombinant DNA techniques for protein production is set forth in the editorial and supporting papers in Vol. 196 of Science (April 1977).